B-ALL患儿外周血髓源性抑制细胞的变化及临床意义

目的通过研究急性B淋巴细胞白血病(acute B lymphoblastic leukemia,B-ALL)患儿外周血中髓源性抑制细胞(myeloid-derived suppressor cells,MDSC)数目、亚群比例、主要功能物质变化,探讨MDSC在儿童B-ALL发病中的作用。方法 28例初诊治疗前和完全缓解后B-ALL患儿作为试验组,按照危险度分为高危组、中危组及标危组,15例健康儿童作为正常对照组,采用流式细胞术(flow cytometric method,FCM)检测各组外周血中MDSC(CD11b~+CD33~+)的数量变化;检测单核细胞样MDSC(CD14~+CD11b~+CD33~+)和粒细胞样MDSC(CD15~+CD11b~+CD33~+)两种不同亚群的比例及其变化情况;检测MDSC主要功能物质精氨酸酶1(arginase-1,Arg-1)和活性氧物质(reactive oxygen species,ROS)的表达情况。结果治疗前B-ALL患儿外周血中MDSC数量比例(2.41%±0.45%)高于完全缓解后(1.56%±0.44%)及正常对照组(0.68%±0.16%)(P0.01);且MDSC数量比例与不同危险度分层呈正相关(r_s=0.680,P0.01),不同危险度分层间MDSC的数量比例差异也具有统计学意义(P0.01);治疗前B-ALL外周血MDSC亚群以粒细胞样MDSC(granulocyte-MDSC,G-MDSC)为主,完全缓解后B-ALL患儿与正常对照外周血中MDSC亚群组成差异无统计学意义(P0.05),且均以单核细胞样MDSC(monocytoid-MDSC,M-MDSC)为主。外周血MDSC中Arg-1和ROS在治疗前B-ALL患儿表达最高(41.00%±9.34%,3 004.26±611.05),完全缓解后次之(24.13%±5.49%,2 031.75±294.01),正常对照组表达最低(10.72%±4.37%,811.33±195.12)(P0.01);Arg-1的表达随ALL危险度分层升高有上升趋势,但差异无统计学意义(P0.05);不同危险度分层中ROS表达差异有统计学意义(P0.01),其中高危组表达高于中危组和标危组,中危和标危组的表达差异无统计学意义(P0.05)。结论 B-ALL患儿外周血中MDSC数量随危险度分层的升高而增加,MDSC可能通过其代谢产物Arg-1及ROS的表达而抑制机体免疫功能,参与儿童B-ALL的发病。

The change and clinical significance of MDSC in the peripheral blood of pediatric B-ALL

Objective To demonstrate changes of myeloid-derived suppressor cells(MDSC) in peripheral blood of children with B-cell acute lymphocytic leukemia (B-ALL),we explore roles of MDSC in pediatric B-ALL.Methods Peripheral blood was collected from 28 cases of newly diagnosed B-ALL pediatric patients,patients with complete remission and 15 cases of health children.Flow cytomertry (FCM) was used to detect number of MDSC (CD11b+CD33 +),proportion of M-MDSC (CD14+CD11b+CD33+) and G-MDSC (CD15+CD11b+CD33+).The expressions of arginase-1 (Arg-1),and reactive oxygen species (ROS) were measured as well.Results The number of MDSC in the B-ALL patients before treatment (2.41％±0.45％) was significantly higher than those after treatment (1.56％±0.44％) and the healthy controls (0.68％± 0.16％) (P＜0.01).There was a positive correlation between the number of MDSC and the risk stratifications (rs=0.680,P＜0.01) and significant difference among the three risk groups was observed (P＜0.01).G-MDSC was the main subtype in the group before the treatment and M-MDSC was the main subtype in the patients with complete remission and the normal controls.The expressions of Arg-1 and ROS were highest in the groups before treatment (41.00％±9.34％,3 004.26±611.05),the second was the groups of complete remission (24.13％±5.49％,2 031.75±294.01) and the healthy controls was the least (10.72％±4.37％,811.33± 195.12) (P＜0.01).Expression of Arg-1 increased by the risk stratifications,but no statistical difference among the three risk groups (P ＞ 0.05).The expression of ROS in the high-risk (HR) group was higher than those in the intermediate-risk (IR) and standard-risk (SR) groups(P＜0.01),no significant difference between the groups of IR and SR (P＞0.05).Conclusion The MDSC increases significantly in the B-ALL patients and is correlated to the risk stratification.Arg-1 and ROS are over expressed in the MDSC from the B-ALL patients.MDSC may play an important role in pathogenesis of B-ALL by immune suppression.